Numerous chemicals encountered in the environment may alter reproductive functions. The rabbit studies ended, after showing that rabbits are less sensitive than humans to the male reproductive toxicity of ethylene dibromide. Additionally, there were no paternally-mediated teratologic effects, as shown by mating, nor was the function of a known number of sperm altered by EDB exposure. Additional studies this year have focused on further characterizing the lesion produced in the testis by boric acid. Previous studies suggested a hormonal component to the testicular atrophy seen after consumption of BA in the feed at 9000 ppm. Studies this year have further evaluated this; initial results from ongoing studies suggest only a small androgenic component. Additionally, we are evaluating the potential involvement of other neuroendocrine-dependent hormonal systems (thyroid, adrenal). Generally, no significant effects have been seen on these other hormone systems. The disposition of BA in selected target and non-target tissues is being determined. The potential of BA to cause in vivo riboflavin deficiency as a mechanism of the testicular toxicity is being investigated, as are the direct effects of BA applied to Sertoli or Leydig cells in primary culture from naive rats. Earlier NIEHS studies found elevated sperm acidic epididymal glycoprotein (AEG) levels; epididymal histology and serum AEG levels, as well as a semi-quantitative immunocytochemistry of AEG will further evaluate this initial finding. Future studies will evaluate the potential hormonal component in the testicular lesion caused by BA at lower doses (2000 ppm), and will compare the lesion development at these two dose rates (9000 vs. 2000).